Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus.

Genome-wide association studies (GWAS) have identified rs11672691 at 19q13 associated with aggressive prostate cancer (PCa). Here, we independently confirmed the finding in a cohort of 2,738 PCa patients and discovered the biological mechanism underlying this association. We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated transcript levels of two biologically plausible candidate genes, PCAT19 and CEACAM21, implicated in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Remarkably, CRISPR/Cas9-mediated single-nucleotide editing showed the direct effect of rs11672691 on PCAT19 and CEACAM21 expression and PCa cellular aggressive phenotype. Clinical data demonstrated synergistic effects of rs11672691 genotype and PCAT19/CEACAM21 gene expression on PCa prognosis. These results provide a plausible mechanism for rs11672691 associated with aggressive PCa and thus lay the ground work for translating this finding to the clinic.

Is There a Bias Towards Males in the Diagnosis of Autism? A Systematic Review and Meta-Analysis.

Autism is more frequently diagnosed in males, with evidence suggesting that females are more likely to be misdiagnosed or underdiagnosed. Possibly, the male/female ratio imbalance relates to phenotypic and camouflaging differences between genders. Here, we performed a comprehensive approach to phenotypic and camouflaging research in autism addressed in two studies. First (Study 1 - Phenotypic Differences in Autism), we conducted a systematic review and meta-analysis of gender differences in autism phenotype. The electronic datasets Pubmed, Scopus, Web of Science, and PsychInfo were searched. We included 67 articles that compared females and males in autism core symptoms, and in cognitive, socioemotional, and behavioural phenotypes. Autistic males exhibited more severe symptoms and social interaction difficulties on standard clinical measures than females, who, in turn, exhibited more cognitive and behavioural difficulties. Considering the hypothesis of camouflaging possibly underlying these differences, we then conducted a meta-analysis of gender differences in camouflaging (Study 2 - Camouflaging Differences in Autism). The same datasets as the first study were searched. Ten studies were included. Females used more compensation and masking camouflage strategies than males. The results support the argument of a bias in clinical procedures towards males and the importance of considering a 'female autism phenotype'-potentially involving camouflaging-in the diagnostic process.

An improved protocol for bacteria identification by MALDI-TOF MS directly from positive blood cultures.

FASTinov® developed a rapid antimicrobial susceptibility test that includes the purification of a bacterial suspension directly from positive blood cultures (BC). In order to streamline laboratory workflow, the use of the bacterial suspension obtained through FASTinov® sample prep was tested for identification (ID) by matrix absorption laser deionization-time of flight mass spectrometry (MALDI-TOF MS) (Bruker) in 364 positive BC, and its accuracy assessed comparing with the MALDI-TOF MS ID of the next-day subcultured colonies. FASTinov sample prep was highly reliable for rapid ID directly from BC with proportion of agreement of 94.9% for Gram-positive and 96.3% for Gram-negative bacteria.

Effect of Three Chemical Agents on Stain Removal from Dentin Caries Lesions Treated with Silver Diamine Fluoride.

INTRODUCTION: This in vitro study aimed to evaluate the effect of three different chemical agents on stain removal and mineral uptake of artificial dentin caries (ADC) lesions treated with silver diamine fluoride (SDF). METHODS: Baseline L*a*b* values were determined in polished human permanent dentin blocks, and ADC lesions were induced with an acid gel for 1 week. Samples were assigned to four groups; in three groups, half of each sample received SDF (30% SDF for 3 min), while the other half received SDF followed by a bleaching treatment protocol (garlic extract, bentonite, or 35% hydrogen peroxide). The fourth group had one SDF-treated half and one half without SDF. Color changes (ΔE) were measured by spectrometry, and transversal microradiography was used to quantify integrated mineral loss (ΔZ) 24 h after treatment (SDF or SDF + bleaching). A two-way mixed ANOVA was applied to thirty percent. RESULTS: SDF application increased mineral uptake by ADC (p = 0.001). The type of chemical agent evaluated (p < 0.0001), time (p = 0.01), and their interaction (p < 0.0001) bleached the ADC treated with SDF. However, 35% hydrogen peroxide was the only compound with a bleaching effect (p < 0.001), without returning to baseline color. None of the compounds altered the mineral uptake effect of SDF (p = 0.30). CONCLUSION: This in vitro study showed mineral uptake effect in ACD within 24 h after SDF application and the ability of hydrogen peroxide to partially remove (reduction of 24%) the staining caused by SDF without affecting its mineral uptake effect.

Efficacy and safety of the dual GIP and GLP-1 receptor agonist tirzepatide for weight loss: a meta-analysis of randomized controlled trials.

OBJECTIVES: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes. We performed a meta-analysis to assess tirzepatide's weight reduction efficacy and safety. METHODS: We searched PubMed, Embase, and Cochrane for randomized controlled trials published from inception to July 2022, comparing tirzepatide with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratio (OR) were calculated for continuous and binary outcomes, respectively. Review Manager 5.4.1 and RStudio were used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. RESULTS: Of 397 search results, 6 studies (4036 participants) ranging from 12 to 72 weeks were included. Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of -7.7 kg (95% CI -11.0, -4.4; p < 0.001), -11.6 kg (95% CI -18.8, -4.3; p = 0.002), and -11.8 kg (95% CI -17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of -8.1% (95% CI -11.0, -5.2; p < 0.001), -11.9% (95% CI -18.1, -5.6; p < 0.001), and -12.4% (95% CI -17.2, -7.5; p < 0.001), respectively. Tirzepatide also reduced BMI and waist circumference. Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo. CONCLUSIONS: The results support that tirzepatide leads to substantial weight reduction and constitutes a valuable therapeutic option for weight management, despite an increase in gastrointestinal symptoms. PROTOCOL REGISTRATION: CRD42022348576.

Auditory Test of Processing Speed: Preliminary validation of a smartphone-based test of mental speed.

BACKGROUND: The Symbol Digit Modalities Test (SDMT) is a gold-standard measure of cognitive efficiency and processing speed for people with multiple sclerosis (PwMS) but relies on vision and oculomotor function. OBJECTIVES: To develop and validate a new processing speed test with minimal memory involvement and no eye function requirements. METHODS: We created an Auditory Test of Processing Speed (ATOPS). A total of 122 PwMS, of whom 33 were severely disabled (median Expanded Disability Status Scale 8.0) and 37 healthy volunteers (HVs), were enrolled. We assessed sensitivity to discriminate MS participants from HVs, convergent validity between ATOPS and SDMT, sensitivity to discriminate between cognitively impaired (CI) and cognitively preserved (CP) MS participants, and correlations with MS pathology (overall brain lesion burden). Acceptability was examined with completion rates and participant ratings of ATOPS. RESULTS: ATOPS discriminated PwMS from HVs (d = 0.739-0.856), correlated with SDMT (|r| = 0.528-0.587), discriminated between CI and CP PwMS (d = 0.623-0.776), and correlated with lesion burden (r = 0.332-0.436). All groups indicated high favorability of ATOPS and severely disabled MS patients could be assessed by ATOPS more frequently than by SDMT (100% vs. 72.4% completion). CONCLUSIONS: ATOPS is a novel, accessible, and acceptable cognitive processing speed test that may be useful in clinical and/or research settings.

Safety and efficacy of topical nitric oxide-releasing berdazimer gel for molluscum contagiosum clearance: A systematic review and meta-analysis of randomized controlled trials.

Molluscum contagiosum (MC) is a contagious infection that, although benign, can become an aesthetic burden and lead to other opportunistic infections, secondary dermatitis, and self-isolation. Currently, several treatment options are available for MC, including the newly investigated nitric oxide-releasing berdazimer gel, leading this review to evaluate randomized controlled trials (RCT) comparing berdazimer gel with a vehicle for treating MC. The meta-analysis included three reports and four RCT involving 1854 patients, with 1106 (59.6%) randomized to receive berdazimer. Our findings suggest that berdazimer is effective in the management of MC lesions, but the increased clearance of lesions and reduction of scarring must be weighed against the potential for topical adverse effects, particularly when considering the use of this therapy in pediatric patients.

SAG3 Toxoplasma gondii cloning reveals unexpected fivefold infection in the blood of feral cats in the Mexican Caribbean.

BACKGROUND: Currently, more than 300 genotypes of Toxoplasma gondii (T. gondii) have been described throughout the world, demonstrating its wide genetic diversity. The SAG3 locus is one of the genes included in the genotyping panel of this parasite. It is associated with its virulence since it participates during the invasion process of the host cells. Therefore, cloning, sequencing, and bioinformatic analysis were used to deepen the understanding of the SAG3 locus genetic diversity of T. gondii in blood samples from feral cats. RESULTS: Six different SAG3 sequences were detected, five of which were detected in one feline. Three sequences were first reported here; one of them was an intragenic recombinant. In the cladogram, four out of ten SAG3 sequences did not share nodes with others reported worldwide. CONCLUSIONS: Cloning and sequencing of samples with more than one restriction pattern by PCR-RFLP were very helpful tools to demonstrate the presence of more than three genotypes of T. gondii in the blood of feral cats from southeastern Mexico. This suggests a potential mixed infection of multiple T. gondii strains and high genetic diversity of the parasites in felines in this tropical region of Mexico.

Shorter versus longer duration of Amoxicillin-based treatment for pediatric patients with community-acquired pneumonia: a systematic review and meta-analysis.

Streptococcus pneumoniae is the most common typical bacterial cause of pneumonia among children. The World Health Organization (WHO) recommends a 5-day Amoxicillin-based empiric treatment. However, longer treatments are frequently used. This study aimed to compare shorter and longer Amoxicillin regimens for children with uncomplicated community-acquired pneumonia (CAP). A search of PubMed, EMBASE, and Cochrane Central was conducted to identify randomized controlled trials (RCTs) comparing 5-day and 10-day courses of Amoxicillin for the treatment of CAP in children older than 6 months in an outpatient setting. Studies involving overlapping populations, lower-than-standard antibiotic doses, and hospitalized patients were excluded. The outcome of interest was clinical cure. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed using the Cochran Q test and I2 statistics. Two independent authors conducted the critical appraisal of the included studies according to the RoB-2 tool for assessing the risk of bias in randomized trials, and disagreements were resolved by consensus. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool to evaluate the certainty of evidence of our results. Three RCTs and 789 children aged from 6 months to 10 years were included, of whom 385 (48.8%) underwent a 5-day regimen. Amoxicillin-based therapy was used in 774 (98%) patients. No differences were found between 5-day and 10-day therapy regarding clinical cure (RR 1.01; 95% CI 0.98-1.05; p = 0.49; I2 = 0%). Subgroup analysis of children aged 6-71 months showed no difference in the rates of the same outcome (RR 1.01; 95% CI 0.98-1.05; p = 0.38; I2 = 0%). The GRADE tool suggested moderate certainty of evidence. CONCLUSION: These findings suggest that a short course of Amoxicillin (5 days) is just as effective as a longer course (10 days) for uncomplicated CAP in children under 10 years old. Nevertheless, generalizations should be made with caution considering the socioeconomic settings of the studies included.PROSPERO Identifier: CRD42022328519. WHAT IS KNOWN: • In the outpatient setting, a few international guidelines recommend a 10-day Amoxicillin course as first-line treatment for community-acquired pneumonia (CAP). • Recent trials have shown that shorter courses of Amoxicillin may be as effective as 10-day regimens in uncomplicated pneumonia. WHAT IS NEW: • When comparing 5-day to 10-day Amoxicillin regimens, evidence suggests no significant difference in clinical cure rates for uncomplicated CAP in outpatient settings. • Generalizations should be made with caution considering the socioeconomic context of the population within the included studies.

Cortical auditory evoked potentials in 1-month-old infants predict language outcomes at 12 months.

The neurophysiological assessment of infants in their first developmental year can provide important information about the functional changes of the brain and supports the study of behavioral and developmental characteristics. Infants' cortical auditory evoked potentials (CAEPs) reflect cortical maturation and appear to predict subsequent language abilities. This study aimed to identify CAEP components to two auditory stimulus intensities in 1-month-old infants and to understand how these are associated with social interactive and self-regulatory behaviors. In addition, it examined whether CAEPs predicted developmental outcomes when infants were assessed at 12 months of age. At 1 month, P2 and N2 components were present for both auditory stimulus intensities, with an increased P2 amplitude being observed for the higher-intensity stimuli. We also observed that an increased P2 amplitude in the lower intensity predicted receptive and expressive language competencies at 12 months. These results are consistent with previous findings indicating an association between auditory processing and developmental outcomes in infants. This study suggests that specific auditory neurophysiological markers are associated with developmental outcomes in the first developmental year.

Therapeutic Vaccines for HPV-Associated Oropharyngeal and Cervical Cancer: The Next De-Intensification Strategy?

The rise in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has prompted a quest for further understanding of the role of high-risk HPV in tumor initiation and progression. Patients with HPV-positive OPSCC (HPV+ OPSCC) have better prognoses than their HPV-negative counterparts; however, current therapeutic strategies for HPV+ OPSCC are overly aggressive and leave patients with life-long sequalae and poor quality of life. This highlights a need for customized treatment. Several clinical trials of treatment de-intensification to reduce acute and late toxicity without compromising efficacy have been conducted. This article reviews the differences and similarities in the pathogenesis and progression of HPV-related OPSCC compared to cervical cancer, with emphasis on the role of prophylactic and therapeutic vaccines as a potential de-intensification treatment strategy. Overall, the future development of novel and effective therapeutic agents for HPV-associated head and neck tumors promises to meet the challenges posed by this growing epidemic.

Assessment of S1-, S2-, and NCP-Specific IgM, IgA, and IgG Antibody Kinetics in Acute SARS-CoV-2 Infection by a Microarray and Twelve Other Immunoassays.

In this study, we comprehensively analyzed multispecific antibody kinetics of different immunoglobulins in hospitalized patients with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Three hundred fifty-four blood samples longitudinally obtained from 81 IgG-seroconverting progressed coronavirus disease 2019 (CoVID-19) patients were quantified for spike 1 (S1), S2, and nucleocapsid protein (NCP)-specific IgM, IgA, IgG, and total Ig antibodies using a microarray, 11 different enzyme-linked immunosorbent assays (ELISAs)/chemiluminescence immunoassays (CLIAs), and 1 rapid test by seven manufacturers. The assays' specificity was assessed in 130 non-CoVID-19 pneumonia patients. Using the microarray, NCP-specific IgA and IgG antibodies continuously displayed higher detection rates during acute CoVID-19 than S1- and S2-specific ones. S1-specific IgG antibodies, however, reached higher peak values. Until the 26th day post-symptom onset, all patients developed IgG responses against S1, S2, and NCP. Although detection rates by ELISAs/CLIAs generally resembled those of the microarray, corresponding to the target antigen, sensitivities and specificities varied among all tests. Notably, patients with more severe CoVID-19 displayed higher IgG and IgA levels, but this difference was mainly observed with S1-specific immunoassays. In patients with high SARS-CoV-2 levels in the lower respiratory tract, we observed high detection rates of IgG and total Ig immunoassays with a particular rise of S1-specific IgG antibodies when viral concentrations in the tracheal aspirate subsequently declined over time. In summary, our study demonstrates that differences in sensitivity among commercial immunoassays during acute SARS-CoV-2 infection are only partly related to the target antigen. Importantly, our data indicate that NCP-specific IgA and IgG antibodies are detected earlier, while higher S1-specific IgA antibody levels occur in severely ill patients.

Assembly of the ß4-Integrin Interactome Based on Proximal Biotinylation in the Presence and Absence of Heterodimerization.

Integrin-mediated laminin adhesions mediate epithelial cell anchorage to basement membranes and are critical regulators of epithelial cell polarity. Integrins assemble large multiprotein complexes that link to the cytoskeleton and convey signals into the cells. Comprehensive proteomic analyses of actin network-linked focal adhesions (FA) have been performed, but the molecular composition of intermediate filament-linked hemidesmosomes (HD) remains incompletely characterized. Here we have used proximity-dependent biotin identification (BioID) technology to label and characterize the interactome of epithelia-specific ß4-integrin that, as α6ß4-heterodimer, forms the core of HDs. The analysis identified ∼150 proteins that were specifically labeled by BirA-tagged integrin-ß4. In addition to known HDs proteins, the interactome revealed proteins that may indirectly link integrin-ß4 to actin-connected protein complexes, such as FAs and dystrophin/dystroglycan complexes. The specificity of the screening approach was validated by confirming the HD localization of two candidate ß4-interacting proteins, utrophin (UTRN) and ELKS/Rab6-interacting/CAST family member 1 (ERC1). Interestingly, although establishment of functional HDs depends on the formation of α6ß4-heterodimers, the assembly of ß4-interactome was not strictly dependent on α6-integrin expression. Our survey to the HD interactome sets a precedent for future studies and provides novel insight into the mechanisms of HD assembly and function of the ß4-integrin.

The association of social skills and behaviour problems with bullying engagement in Portuguese adolescents: From aggression to victimization behaviors.

This study examines sex differences regarding social skills, behavior problems and bullying engagement, and the association of social skills and behavior problems with bullying engagement, in adolescents. Participants were 447 Portuguese adolescents (252 girls and 195 boys) aged between 12 and 19-years-old. Social skills and behavior problems were assessed using the self-report version of Social Skills Improvement System - Rating Scales. Bullying engagement was assessed using the Scale of Interpersonal Behavior at School. Girls scored higher on social skills and reported more internalizing and fewer externalizing problems than boys, whereas boys reported more aggressive verbal behaviors than girls. Adolescents exhibiting fewer social skills and more internalizing and externalizing problems engage more frequently in bullying aggressive behaviors. In addition, adolescents presenting more internalizing and externalizing problems are more often victimized by bullies. Furthermore, boys more frequently engage in bullying aggressive and victimization behaviors, whereas younger adolescents with more social skills tend to engage less frequently in bullying aggressive behaviors.

Contributions of infant vagal regulation at 1 month to subsequent joint attention abilities.

Since birth, humans develop an ability to regulate their inner states and behaviors, when facing demanding situations, in order to restore calmness and engage with other persons and the surrounding environment. The present study analyzed whether 1-month infant vagal regulation to auditory stimuli was associated with later joint attention abilities-responding to and initiating joint attention-in interaction with their mothers. Twenty-three infants were assessed and measures of respiratory sinus arrhythmia-RSA (baseline and vagal tone change during auditory stimulation) were used as index of vagal regulation. At 12-months, joint attention behaviors were assessed in a 10-min toy-play mother-infant interaction. Correlational analyses showed that lower baseline RSA and larger increases in vagal tone during auditory stimulation were related to more instances of joint attention behaviors at 12 months, especially responding to joint attention. Results suggest that distinct profiles of autonomic functioning may contribute to joint attention skills.

Understanding transformative capacity to boost urban climate adaptation: A Semi-Systematic Literature Review.

Transformative capacity (TC) is key for addressing climate change impacts. It refers to urban areas' ability for profound and intentional change to address current challenges and move towards a more desirable and resilient state. However, its varied applications across disciplines can lead to misunderstandings and implementation challenges. Thus, this Semi-Systematic Literature Review (SSLR) on TC within urban studies from 2016 to 2022 aims to overview and synthesise TC literature and its gaps to inform ongoing debates, intersecting it with climate-related research. The results show an increasing interest in TC within two fields of knowledge: resilience studies and transformative research. The review found TC as a catalyst for transformative actions, promoting sustainable pathways, enhancing resilience, and driving fundamental changes in urban climate adaptation. Finally, the prevailing literature gaps concern the TC concept's fragmentation, excessive research on governance features, and lack of joint research about TC and innovation.

Effects of optogenetic silencing the anterior cingulate cortex in a delayed non-match to trajectory task.

Working memory is a fundamental cognitive ability, allowing us to keep information in memory for the time needed to perform a given task. A complex neural circuit fulfills these functions, among which is the anterior cingulate cortex (CG). Functionally and anatomically connected to the medial prefrontal, retrosplenial, midcingulate and hippocampus, as well as motor cortices, CG has been implicated in retrieving appropriate information when needed to select and control appropriate behavior. The role of cingulate cortex in working memory-guided behaviors remains unclear due to the lack of studies reversibly interfering with its activity during specific epochs of working memory. We used eNpHR3.0 to silence cingulate neurons while animals perform a standard delayed non-match to trajectory task, and found that, while not causing an absolute impairment in working memory, silencing cingulate neurons during retrieval decreases the mean performance if compared to silencing during encoding. Such retrieval-associated changes are accompanied by longer delays observed when light is delivered to control animals, when compared to eNpHR3.0+ ones, consistent with an adaptive recruitment of additional cognitive resources.

White matter network underlying semantic processing: evidence from stroke patients.

The hub-and-spoke theory of semantic representation fractionates the neural underpinning of semantic knowledge into two essential components: the sensorimotor modality-specific regions and a crucially important semantic hub region. Our previous study in patients with semantic dementia has found that the hub region is located in the left fusiform gyrus. However, because this region is located within the brain damage in patients with semantic dementia, it is not clear whether the semantic deficit is caused by structural damage to the hub region itself or by its disconnection from other brain regions. Stroke patients do not have any damage to the left fusiform gyrus, but exhibit amodal and modality-specific deficits in semantic processing. Therefore, in this study, we validated the semantic hub region from a brain network perspective in 79 stroke patients and explored the white matter connections associated with it. First, we collected data of diffusion-weighted imaging and behavioural performance on general semantic tasks and modality-specific semantic tasks (assessing object knowledge on form, colour, motion, sound, manipulation and function). We then used correlation and regression analyses to examine the association between the nodal degree values of brain regions in the whole-brain structural network and general semantic performance in the stroke patients. The results revealed that the connectivity of the left fusiform gyrus significantly predicted general semantic performance, indicating that this region is the semantic hub. To identify the semantic-relevant connections of the semantic hub, we then correlated the white matter integrity values of each tract connected to the left fusiform gyrus separately with performance on general and modality-specific semantic processing. We found that the hub region accomplished general semantic processing through white matter connections with the left superior temporal pole, middle temporal gyrus, inferior temporal gyrus and hippocampus. The connectivity between the hub region and the left hippocampus, superior temporal pole, middle temporal gyrus, inferior temporal gyrus and parahippocampal gyrus was differentially involved in object form, colour, motion, sound, manipulation and function processing. After statistically removing the effects of potential confounding variables (i.e. whole-brain lesion volume, lesion volume of regions of interest and performance on non-semantic control tasks), the observed effects remained significant. Together, our findings support the role of the left fusiform gyrus as a semantic hub region in stroke patients and reveal its crucial connectivity in the network. This study provides new insights and evidence for the neuroanatomical organization of semantic memory in the human brain.

Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFß1 Signaling to Orchestrate Prostate Cancer Progression.

The extracellular matrix (ECM) undergoes substantial changes during prostate cancer (PCa) progression, thereby regulating PCa growth and invasion. Herein, a meta-analysis of multiple PCa cohorts is performed which revealed that downregulation or genomic loss of ITGA1 and ITGA2 integrin genes is associated with tumor progression and worse prognosis. Genomic deletion of both ITGA1 and ITGA2 activated epithelial-to-mesenchymal transition (EMT) in benign prostate epithelial cells, thereby enhancing their invasive potential in vitro and converting them into tumorigenic cells in vivo. Mechanistically, EMT is induced by enhanced secretion and autocrine activation of TGFß1 and nuclear targeting of YAP1. An unbiased genome-wide co-expression analysis of large PCa cohort datasets identified the transcription factor TEAD1 as a key regulator of ITGA1 and ITGA2 expression in PCa cells while TEAD1 loss phenocopied the dual loss of α1- and α2-integrins in vitro and in vivo. Remarkably, clinical data analysis revealed that TEAD1 downregulation or genomic loss is associated with aggressive PCa and together with low ITGA1 and ITGA2 expression synergistically impacted PCa prognosis and progression. This study thus demonstrated that loss of α1- and α2-integrins, either via deletion/inactivation of the ITGA1/ITGA2 locus or via loss of TEAD1, contributes to PCa progression by inducing TGFß1-driven EMT.

The interplay between climate change and ageing: A systematic review of health indicators.

Climate change and rapid population ageing pose challenges for communities and public policies. This systematic review aims to gather data from studies that present health indicators establishing the connection between climate change and the physical and mental health of the older population (≥ 65 years), who experience a heightened vulnerability to the impacts of climate change when compared to other age cohorts. This review was conducted according to the PICO strategy and following Cochrane and PRISMA guidelines. Three databases (PubMed, Scopus and Greenfile) were searched for articles from 2015 to 2022. After applying inclusion and exclusion criteria,nineteen studies were included. The findings indicated that various climate change phenomena are associated with an elevated risk of mortality and morbidity outcomes in older adults. These included cardiovascular, respiratory, renal, and mental diseases, along with physical injuries. Notably, the impact of climate change was influenced by gender, socioeconomic status, education level, and age-vulnerability factors. Climate change directly affected the health of older adults through ambient temperature variability, extreme and abnormal temperatures, strong winds, sea temperature variability, extreme El Niño-southern Oscillation (ENSO) conditions and droughts, and indirectly by air pollution resulting from wildfires. This review presents further evidence confirming that climate change significantly impacts the health and well-being of older adults. It highlights the urgency for implementing effective strategies to facilitate adaptation and mitigation, enhancing the overall quality of life for all individuals.